1. Technical Field
The present invention relates to an animal model for infant pathologies including a model for infants in a neonatal intensive care unit (NICU) setting. More particularly, the present invention relates to a non-human animal model which may be used as a model of retinopathy of prematurity (ROP) as well as for other NICU applications. The invention includes both the non-human models and the process for making specific models.
2. Background Art
There are currently a variety of animal models useful for the study and analysis of diseases as they pertain to humans. Generally, animal models are non-human animals having some type of disease, genetic alteration or conditioning so that the model displays a pathology or ailment similar to a human condition. Through the use of animal models, observations, studies and research may be conducted on diseases and other conditions using methods which might be considered inappropriate for use on humans. Ideally, such science may cultivate new procedures and treatments for humans based upon studies and experiment with the animal models.
For an animal to serve as a useful model, the disease or pathology that the animal model has must be similar in etiology and function to the human equivalent disease or pathology. As different animals display different similarities and dissimilarities to humans, care must be taken in selecting the appropriate animal model for a specific human disease. With this understood, providing the appropriate animal models for the variety of diseases afflicting humans have fostered a great interest. For example, in Falk et al. (U.S. Pat. No. 5,625,124) a transgenic non-human animal is disclosed as a model for the H. pylori infection of epithelial cells of the stomach and small intestines. According to Falk et al. the transgenic mouse may be made by constructing a transgene which includes a gut epithelial cell specific promoter and a nucleotide sequence encoding a human fucosyltransferase. The model is also described for use in screening and evaluating compounds which block H. pylori adhesion to the gut endothelium or ameliorate the effects of H. pylori binding on the pathogenesis of acid peptide disease.
In published U.S. Patent Application No. US 2004/0191170 issued to Mond et al., an animal model is disclosed for evaluating infections caused by enteric pathogens, including diarrheagenic Escherichia coli, such as enterotoxigenic, enterohemorrhagic, Shiga-toxin producing, and interopathogenic E. coli. The animal model is described as preferably useful for evaluating the efficacy of vaccines and therapeutic agents against enteric bacterial infections as well as for enteric viral infections. Furthermore, Mond et al. describes suitable animals for the animal model as including rodents and rodent like animals such as mice, hamsters, rabbits, guinea pigs, ferrets, chinchillas, and rats.
Tirabassie et al. (published U.S. Patent Application No. US 2006/0179499) provides methods for generating a non-human animal model for a diabetic complication. Generally, animals are administered a TLR agonist in an amount sufficient to induce at least one diabetic complication. Tirabassie et al. further describes an additional aspect of the invention as a method of screening for a therapeutic agent for treating or preventing a diabetic complication which involves the use of a test animal in comparison to a control animal wherein the test animal is provided with at least one diabetic complication and compared to the control animal throughout trials with a therapeutic agent.
In published U.S. Patent Application No. US 2007/0079390 to Rajakumar et al., an animal model is provided which is described as exhibiting neuropathological and behavioral features associated with human schizophrenia. The schizophrenia animal model as described by Rajakumar et al., is made by a method comprising the premature elimination of subplate cells in the developing prefrontal cerebral cortex of the animal.
According to Aquilina et al. in “A Neonatal Piglet Model Of Intraventricular Hemorrhage And Posthemorrhagic Ventricular Dilation,” JOURNAL OF NEUROSURGERY: PEDIATRICs, Vol. 107, pages 126-130 (2007), piglets are created to replicate human neonatal intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation (PHVD). Such models allow for physiological and ultrasonographic monitoring over a prolonged survival period so as to evaluate both non-invasive and surgical options in the management of both IVH and PHVD in young humans.
One area in which there has been minimal research with animal models is in simulating the conditions of an infant within a neonatal intensive care unit (NICU). NICUs typically specialize in the care of ill or preterm newborn infants by use of specialized equipment and unique technologies. In addition to prematurity, NICUs provide treatment for infants with diseases including perinatal asphyxia, major birth defects, sepsis, respiratory distress syndrome, hypoxia, intraventricular hemorrhage, neonatal seizures, brain insult, neurodegeneration, and retinopathy of prematurity and the like.
In particular, retinopathy of prematurity (ROP) afflicts over 300,000 infants worldwide. In attempts to both treat and inhibit ROP which can potentially lead to blindness, technologies have been created for the disease. Specifically, in U.S. Pat. No. 5,336,248, issued to Good et al, an apparatus for the treatment or inhibition of retinopathy of prematurity is provided which provides substantially red light having a wave band of approximately 612 nanometers to the infant. As a result the infant is restricted to red light which Good et al. believes is beneficial in the treatment of the disease.
In Neu et al (U.S. Pat. No. 7,148,199), dipeptides are administered which may prevent retinal blood vessel damage, a common characteristic of retinopathy. Moreover, Neu et al. describes the use of peptides as preventing the proliferation of abnormal blood vessels through the administration of arginine and glutamine typically in an aqueous solution.
Despite there being a variety of animal models specific to different human diseases, there are few, if any, animal models available for pathologies associated with infants in a NICU. Rather, the majority of animal models is linked to adult diseases and only occasionally correlates to infant conditions of the same disease. In addition, there are few resources available for the study of ROP even though the disease affects thousands of infants.
What is desired therefore is an animal model that could be used for simulating the conditions of various diseases that afflict human infants. In addition, there is a need for an animal model which simulates ROP. Further desired is an animal model which may be used to mimic diseases of infants that are characterized as NICU applications. Indeed, a combination of characteristics including an animal model which replicates ROP of a human infant provides an animal model useful as a tool in both observing and treating pathologies of infants that are treated in the NICU.